kn-93 and ifenprodil

Calcium entry through postsynaptic NMDA-Rs and subsequent activation of CaMKII trigger synaptic plasticity in many brain regions. Active CaMKII can bind to NMDA-Rs, but the physiological role of this interaction is not well understood. Here, we test if association between active CaMKII and synaptic NMDA-Rs is required for synaptic plasticity. Switching synaptic NR2B-containing NMDA-Rs that bind CaMKII with high affinity with those containing NR2A, a subunit with low affinity for CaMKII, dramatically reduces LTP. Expression of NR2A with mutations that increase association to active CaMKII recovers LTP. Finally, driving into synapses NR2B with mutations that reduce association to active CaMKII prevents LTP. Spontaneous activity-driven potentiation shows similar results. We conclude that association between active CaMKII and NR2B is required for different forms of synaptic enhancement. The switch from NR2B to NR2A content in synaptic NMDA-Rs normally observed in many brain regions may contribute to reduced plasticity by controlling the binding of active CaMKII.

Topics: Animals; Animals, Newborn; Benzylamines; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Cell Line; Cricetinae; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Gene Expression; Green Fluorescent Proteins; Hippocampus; In Vitro Techniques; Magnesium; Membrane Potentials; Mutagenesis; Neuronal Plasticity; Neurons; Patch-Clamp Techniques; Piperidines; Protein Binding; Protein Kinase Inhibitors; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Sulfonamides; Synapses; Time Factors; Transfection